Operable Colorectal Cancer Research Articles

Detection of DNA methylation markers in plasma cell-free DNA of patients with operable colorectal cancer

Detection of DNA methylation markers in plasma cell-free DNA of patients with operable colorectal cancer

Histopathological tumour microenvironment score independently predicts outcome in primary operable colorectal cancer.

Colorectal cancer (CRC) is a heterogenous malignancy and research is focused on identifying novel ways to subtype patients. In this study, a novel classification system, tumour microenvironment score (TMS), was devised based on Klintrup-Mäkinen grade (KMG), tumour stroma percentage (TSP), and tumour budding. TMS was performed using a haematoxylin and eosin (H&E)-stained section from retrospective CRC discovery and validation cohorts (n = 1,030, n = 787). TMS0 patients had high KMG, TMS1 were low for KMG, TSP, and budding, TMS2 were high for budding, or TSP and TMS3 were high for TSP and budding. Scores were assessed for association with survival and clinicopathological characteristics. Mutational landscaping and Templated Oligo-Sequencing (TempO-Seq) profiling were performed to establish differences in the underlying biology of TMS. TMS was independently prognostic in both cohorts (p < 0.001, p < 0.001), with TMS3 predictive of the shortest survival times. TMS3 was associated with adverse clinical features including sidedness, local and distant recurrence, higher T stage, higher N stage, and presence of margin involvement. Gene set enrichment analysis of TempO-Seq data showed higher expression of genes associated with hallmarks of cancer pathways including epithelial to mesenchymal transition (p < 0.001), IL2 STAT5 signalling (p = 0.007), and angiogenesis (p = 0.017) in TMS3. Additionally, enrichment of immunosuppressive immune signatures was associated with TMS3 classification. In conclusion, TMS represents a novel and clinically relevant method for subtyping CRC patients from a single H&E-stained tumour section.

Clinicopathological features of colon cancer depending on the dMMR status of the tumor

Aim. To conduct a clinical and morphological assessment of the characteristics of colon cancer depending on the dMMR / pMMR status of the tumor.Materials and methods. A retrospective study included 66 patients with operable colorectal cancer (CRC) (T1-4bN0-2bM1), who were treated at Cancer Research Institute of Tomsk National Research Medical Center (NRMC). The average age of the patients was 64.4 ± 12.8 years. All patients underwent hemicolectomy or colon resection, as well as intraoperative resection of distant metastases, if present.Results. We determined that in CRC patients with pMMR tumors, hematogenous metastases were detected in 27.3% of cases, while in patients with dMMR tumors, hematogenous metastases were detected only in 6.1% of cases (p = 0.021). A comparative analysis of dMMR and pMMR tumors also allowed to establish higher frequency of perineural invasion among the pMMR subgroup of carcinomas (p = 0.039). The sign of tumor budding was found both in dMMR carcinomas (36%) and in pMMR tumors (45%). This sign was associated with damage to regional lymph nodes (p = 0.0017). A more detailed analysis of the tumor budding phenomenon showed that in dMMR tumors, Bd1 low-grade budding (83%) predominated. In pMMR tumors, Bd2 intermediate-grade budding (33%) and Bd3 high-grade budding (26.7%) prevailed. Bd2 and Bd3 tumor budding types were associated with hematogenous metastasis (p &lt; 0.001).Conclusion. The obtained data demonstrate the differences in such pathomorphological parameters as perineural invasion and the degree of tumor budding depending on the dMMR / pMMR status of the tumor. These histologic parameters in tumor tissue are also associated with higher incidence of distant metastasis in patients with pMMR carcinomas as opposed to patients with dMMR tumors.

949 ‘Host Stage Migration’ in Newly Diagnosed, Operable Colorectal Cancer During the First Wave of the COVID-19 Pandemic – A Multicentre Comparative Cohort Study

Abstract Aim The COVID-19 pandemic caused immeasurable disruption to cancer pathways across the United Kingdom, resulting in many patients presenting with more advanced stages of disease. This study explores whether migration of ‘host-stage’ was evident amongst patients who underwent resection for colorectal cancer during this period. Method Consecutive patients who underwent a potentially curative resection, for colorectal cancer newly diagnosed between 23/03/2020 and 23/12/2020, were identified from prospectively maintained databases. A cohort from the same dates in 2019 were sought for comparison. CT body composition analysis, at the L3 vertebral level, allowed calculation of skeletal muscle index (SMI) and density (SMD). Neutrophil-lymphocyte-ratio (NLR) was selected as a composite marker of systemic inflammation. The primary outcomes of interest were host body composition and systemic inflammatory response. Results Overall, 280 patients underwent a colorectal resection during 9-month periods in the COVID-19 pandemic (n = 117) and preceding year (n = 167). Age, ASA, sex, and tumour location were all comparable between cohorts. More patients in the COVID cohort had a T3/4 malignancy (83.6% vs. 67.7%, p = 0.04). Median SMI (42.4 vs. 44.3cm2/m2) and SMD (33.6 vs. 33.1 HU) were similar in COVID and pre-COVID populations. NLR was higher amongst patients during the pandemic (median 3.6, IQR: 2.2-5.8) than those in the previous year (median 3.3, IQR: 2.1-4.6, p = 0.05). Conclusions A higher proportion of patients who underwent resection of a colorectal cancer during the COVID pandemic had a locally advanced tumour. While CT-body composition was comparable between cohorts, higher levels of pre-treatment systemic inflammation were evident. This may be suggestive of ‘host-stage’ migration.

The relationship between heart rate variability and TNM stage, co-morbidity, systemic inflammation and survival in patients with primary operable colorectal cancer

High vagal nerve activity, reliability measured by HRV, is considered protective in cancer, reducing oxidative stress, inflammation and opposing sympathetic nerve activity. The present monocentric study examines the relationship between HRV, TNM stage, co-morbidity, systemic inflammation and survival in patients who underwent potentially curative resections for colorectal cancer (CRC). Time-domain HRV measures, Standard Deviation of NN-intervals (SDNN) and Root Mean Square of Successive Differences (RMSSD), were examined as categorical (median) and continuous variables. Systemic inflammation was determined using systemic inflammatory grade (SIG) and co-morbidity using ASA. The primary end point was overall survival (OS) and was analysed using Cox regression. There were 439 patients included in the study and the median follow-up was 78 months. Forty-nine percent (n = 217) and 48% (n = 213) of patients were categorised as having low SDNN (< 24 ms) and RMSSD (< 29.8 ms), respectively. On univariate analysis, SDNN was not significantly associated with TNM stage (p = 0.830), ASA (p = 0.598) or SIG (p = 0.898). RMSSD was not significantly associated with TNM stage (p = 0.267), ASA (p = 0.294) or SIG (p = 0.951). Neither SDNN or RMSSD, categorical or continuous, were significantly associated with OS. In conclusion, neither SDNN or RMSSD were associated with TNM stage, ASA, SIG or survival in patients undergoing potentially curative surgery for CRC.

The impact of metformin on survival in diabetes patients with operable colorectal cancer: A nationwide retrospective cohort study

To investigate the impact of metformin on survival of diabetic patients following surgery for colorectal cancer (CRC). This was a retrospective cohort study. From Taiwan's population-based National Health Insurance Research Database (NHIRD) we identified 12,512 patients with CRC and type II diabetes who underwent curative surgery between 2000 and 2012. Of these, 6222 patients were included in a matched cohort. Using Cox regression models with time-dependent covariates we examined the impact of metformin on survival. Average duration of follow-up was 49 and 54 months for metformin users and non-users, respectively. Cox proportional hazard model showed that metformin was associated with 5-year overall survival benefit (Hazard ratio, 0.23 [95% CI, 0.20-0.26]) and inverse association with risk of liver metastasis (Hazard ratio, 0.79 [95% CI, 0.68-0.93]). Metformin was associated with a survival benefit in diabetic patients with CRC following surgery, and an inverse association with risk of liver metastases suggesting a potential anti-tumorigenic effect.

Survival and Prognostic Factors Predicting Outcomes of Patients with Primary Non-Metastatic Colorectal Cancer who have not had Curative Intervention

Abstract Background: The natural progression and life expectancy of patients following a diagnosis of treatable colorectal cancer who receive only symptomatic treatment, nonoperative palliative therapy, or noncurative surgical interventions are relatively unknown. Objectives: The objective of this retrospective study was to examine the survival of patients following a diagnosis of primary nonmetastatic colorectal cancer who did not undergo major surgery for the purpose of curative treatment. Design: A retrospective observational study. Study Settings: Department of Colorectal Surgery, King’s College Hospital, London. Patient and Methods: A retrospective study of patients with stages I–III colorectal cancer who had not undergone noncurative surgery, palliative chemotherapy, or radiotherapy between 2012 and 2019 was conducted. Multivariate and univariate analyses were used to evaluate the prognostic factors associated with overall survival (OS). Main Outcome Measure: OS. Sample Size: A total of 78 patients. Results: A total of 78 patients were enrolled in this study. The median survival rate was 296 days or 9.7 months, and the mean survival rate was 385 days (15–1894 days). The 1- and 2-year OS rates were 37.2% and 3.8%, respectively. Univariate analysis revealed that three parameters were statistically significant for OS with a significant correlation with performance status (PS) (P = 0.004), tumor stage (pT) (P = 0.030), and lymph node metastasis (pN) (P = 0.001). Multivariate analysis revealed that pN2 (hazard ratio: 2.19, 95% confidence index: -1.1–4.4) and PS 3 and 4 (hazard ratio: 0.525, 95% confidence index: 0.3–1.0, P = 0.026) were prognostic factors associated with OS. Conclusion: Operable colorectal cancer patients without surgical resection have an OS rate of &lt;1 year; a higher T and N stage is associated with adverse prognosis. Limitations: Our study is limited by its retrospective nature and small sample size. In addition, patients underwent various palliative interventions based on their unique clinical, pathological, and social needs. Conflict of Interest: The authors have no conflict of interest to declare.

EGS P24 Extended Thromboprophylaxis in the Prevention of Postoperative Venous Thromboembolism after Emergency Surgery

Abstract Background Venous thromboembolism (VTE) after emergency laparotomy is a significant cause of morbidity and mortality. Where extended thromboprophylaxis is used in the post-operative care of patients with colorectal malignancy or pelvic surgery, no such guideline exists for the patient undergoing emergency laparotomy. Arguably emergency laparotomy has one of the highest associated death rates of all types of surgery, greater than that of major elective GI surgery and involves high risk patients. The objective of this study is to ascertain the incidence of symptomatic VTE after emergency laparotomy within current thromboprophylaxis regimens at a district general hospital and consider the benefits of extended regimes in this patient cohort. Methods A database of all patients who underwent emergency laparotomy over a 12 month period from January 2019 to December 2019 was retrospectively analysed. The primary outcome was the incidence of symptomatic VTE within 90 days of emergency laparotomy. This was cross-referenced to known patient risk factors for thromboembolism. Results A total of 113 patients underwent emergency laparotomy during this period. Those who had multiple laparotomies and were duplicated or who died were excluded, leaving a total of 94 patients, 55 female and 39 male. 80 patients underwent a VTE prophylaxis regimen using perioperative and postoperative low-molecular-weight heparin (LMWH) based on their weight. The average length of stay was 18 days. 20 patients had an inpatient stay greater than 28 days and, therefore, received extended prophylaxis during their admission. 21 patients were given prolonged anticoagulation on discharge to complete a total of 28 days, 14 of these had suspected cancer intraoperatively, 6 were previously already anticoagulated. The postoperative VTE incidence was 6, 4 were diagnosed during admission and so received prolonged anticoagulation on discharge. 2 patients were not given prolonged VTE prophylaxis on discharge. Conclusions An extended VTE prophylaxis regimen using low-molecular-weight heparin is simple and effective and an accepted practice in the management of post operative colorectal cancer patients. A randomised control trial is likely needed to further explore the use of extended low molecular weight heparin in the postoperative care of emergency laparotomy patients.

Circulation tumour DNA in predicting recurrence and prognosis in operable colorectal cancer patients: A meta-analysis.

Selecting the appropriate patient for further treatment after surgery and adjuvant chemotherapy (ACT) for colorectal cancer (CRC) can improve the patient's prognosis. Circulating tumour DNA (ctDNA) has the potential to predict recurrence and prognosis after CRC surgery and ACT, but the results are still inconclusive. As the completed studies have small sample sizes and different experimental methods, a meta-analysis was conducted to assess the ctDNA on recurrence and prognosis after CRC surgery and ACT. PubMed, Embase, the Web of Science and the Cochrane Library were searched for potentially eligible studies published up to 6 March 2022. Pooled relative risk (RR) and pooled hazard ratio (HR) were calculated to evaluate recurrence and the prognosis of recurrence-free survival (RFS) following CRC surgery and ACT. Fourteen studies published between 2014 and 2022 included 2393 patients, and 7189 serum samples were eventually included in the meta-analysis. The pooled revealed that ctDNA-positive patients were at high risk of recurrence after CRC surgery (RR=4.43, 95% CI: 3.58-5.48, p < .05) and had a poorer prognosis for RFS (HR=7.26, 95% CI: 5.48-9.62, p < .05). The pooled revealed that ctDNA-positive patients were at high risk of recurrence after ACT (RR=5.77 95% CI: 4.33-7.69, p < .05) and had a poorer prognosis for RFS (HR=13.96, 95% CI: 8.71-22.4, p < .05). ctDNA-positive patients were at a high risk of recurrence after CRC surgery and ACT and had a poorer prognosis. Hence, ctDNA-positive patients required close follow-up and further treatments.

Evaluation of Preoperative Neutrophil-to-Lymphocyte Ratio and Platelet-to-Lymphocyte Ratio for their Predictive Value in Determining Short-Term Mortality in Patients with Operable Colorectal Cancers

Aim: The aim of this study was to investigate whether preoperative neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) have a predictive value in short-term mortality in patients with operable colorectal cancer (CRC). Material and Methods: A total of 231 (93 female, 138 male) patients with operated CRC between 2016 and 2021 in a university hospital were analyzed retrospectively. Median age was 68 (range, 26-92) years and patients had been under follow-up for a median of 25 (range, 0-54) months. Patients were grouped with respect to survival, those who were alive (n=175) and those who died (n=56) during the follow-up. Results: The area under the curve for NLR was 0.649 (95% CI: 0.563-0.734, p=0.001), optimal cut-off was 5.08 and demonstrated a sensitivity of 48.2% and a specificity of 81.7% for predicting mortality. The area under the curve for PLR was 0.635 (95% CI: 0.546-0.723, p=0.002), optimal cut-off was 221.5 and demonstrated a sensitivity of 55.4% and a specificity of 72.0%. Multiple regression analysis revealed that recurrence (OR: 60.910, 95% CI: 9.807-378.319, p=&amp;lt;0.001), leakage (OR: 10.724, 95% CI: 1.281-89.747, p=0.029), high NLR (OR: 3.735, 95% CI: 1.602-8.711, p=0.002) and higher age (OR: 1.136, 95% CI: 1.081-1.193, p&amp;lt;0.001) were independently associated with mortality. Conclusion: The results of this study support studies indicating that preoperative NLR and PLR are effective in predicting short-term mortality in CRC patients who underwent surgical resection. Although further studies are necessary, these biomarkers are promising for future use as prognostic tools in CRC patients.

Nomograms based on lactate dehydrogenase to albumin ratio for predicting survival in colorectal cancer.

Purpose: We aimed to determine if lactate dehydrogenase to albumin ratio (LAR) might play a prognostic role for patients with operable colorectal cancer (CRC).Patients and Methods: 1334 operable CRC patients in Wuhan Union Hospital Between July 2013 and September 2017 were enrolled in this study and were randomly appointed them into training (n=954) and validation (n=380) sets. The relationship between LAR and overall survival (OS) and disease-free survival (DFS) were determined by restricted cubic splines (RCS) with Cox regression models. LAR was then divided into three categories based on the RCS and compared to the well-known TNM stage system. Finally, survival nomograms were developed by compounding the LAR and other clinical factors.Results: Baseline LAR values and the all-cause mortality were U shaped, which slowly decreased until around 4.50 and then started to increase rapidly when the LAR ranged from 4.50-6.68 and then became flat thereafter (P for non-linearity <0.001). LAR was superior to TNM stage for OS as well as DFS and LAR plus TNM stage could add more net benefit than clinical model alone. Moreover, the survival nomograms based on LAR achieved great predictive ability for OS and DFS in operable CRC patients.Conclusions: LAR could be served as a reliable prognostic factor for OS as well as DFS, with more accurate prognostic prediction than current TNM stage for patients with operable CRC.

Tumor budding as a predictive marker for 5-fluorouracil response in adjuvant-treated stage III colorectal cancer.

Tumor budding (TB) has been described as an adverse prognostic marker for operable colorectal cancer (CRC); however, a limited number of studies have demonstrated the prognostic significance of TB in patients with drug therapy. This study was conducted to determine the predictive power of TB in stage III CRC patients who received adjuvant chemotherapy. We retrospectively collected clinicopathological data including TB of 237 stage III colorectal cancer patients at Hiroshima University Hospital between July 1, 2006 and June 31, 2019. Differential disease-free survival (DFS) was investigated according to TB status. This study included 237 patients with a median age of 67years, comprising patients who underwent surgery alone (n = 65), 5-fluorouracil (5-FU) monotherapy (n = 129), and oxaliplatin-based chemotherapy (n = 43). Overall, 81 patients developed disease recurrence, and 33 patients died of cancer-related causes. The TB status was categorized into two groups: 99 with low budding (< 5 buds) and 138 with high budding (≥ 5 buds). Overall, the low budding cases demonstrated significantly better DFS. In the 5-FU monotherapy group, low-risk patients (T1, T2, or T3 and N1) with low budding showed a remarkably higher 3-year DFS (91%) compared to high budding (55%). Our results indicate that TB could play a subsidiary role in selecting patients who could maintain a favorable prognosis with 5-FU monotherapy in stage III CRC.

Relationship between immune checkpoint proteins, tumour microenvironment characteristics, and prognosis in primary operable colorectal cancer.

The tumour microenvironment is an important factor for colorectal cancer prognosis, affecting the patient's immune response. Immune checkpoints, which regulate the immune functions of lymphocytes, may provide prognostic power. This study aimed to investigate the prognostic value of the immune checkpoints TIM‐3, LAG‐3 and PD‐1 in patients with stage I–III colorectal cancer. Immunohistochemistry was employed to detect TIM‐3, LAG‐3, PD‐1 and PD‐L1 in 773 patients with stage I–III colorectal cancer. Immune checkpoint protein expression was assessed in tumour cells using the weighted histoscore, and in immune cells within the stroma using point counting. Scores were analysed for associations with survival and clinical factors. High tumoural LAG‐3 (hazard ratio [HR] 1.45 95% confidence interval [CI] 1.00–2.09, p = 0.049) and PD‐1 (HR 1.34 95% CI 1.00–1.78, p = 0.047) associated with poor survival, whereas high TIM‐3 (HR 0.60 95% CI 0.42–0.84, p = 0.003), LAG‐3 (HR 0.58 95% CI 0.40–0.87, p = 0.006) and PD‐1 (HR 0.65 95% CI 0.49–0.86, p = 0.002) on immune cells within the stroma associated with improved survival, while PD‐L1 in the tumour (p = 0.487) or the immune cells within the stroma (p = 0.298) was not associated with survival. Furthermore, immune cell LAG‐3 was independently associated with survival (p = 0.017). Checkpoint expression scores on stromal immune cells were combined into a Combined Immune Checkpoint Stromal Score (CICSS), where CICSS 3 denoted all high, CICSS 2 denoted any two high, and CICSS 1 denoted other combinations. CICSS 3 was associated with improved patient survival (HR 0.57 95% CI 0.42–0.78, p = 0.001). The results suggest that individual and combined high expression of TIM‐3, LAG‐3, and PD‐1 on stromal immune cells are associated with better colorectal cancer prognosis, suggesting there is added value to investigating multiple immune checkpoints simultaneously.

Rapid screening for individualized chemotherapy optimization of colorectal cancer: A novel conditional reprogramming technology-based functional diagnostic assay.

BackgroundIn vitro patient tumor models such as patient-derived organoids (PDO) and conditionally reprogrammed (CR) cell culture are important for translational research and pre-clinical drug testing. In this study we present a personalized drug sensitivity test for late stage, potentially operable colorectal cancer (CRC) using patient-derived primary tumor cells isolated with i-CR technology, an optimized CR method. We explored the clinical feasibility of using i-CR platform to guide CRC chemotherapy, and established the correlation between in vitro drug sensitivity and patient clinical response. MethodsPrimary CRC tumor cells were isolated and cultured with the i-CR technology. NGS was performed and the WES and CNV results of i-CR cells were compared with that of the original patient tumor samples. In vitro drug screenings were done with guideline chemotherapy drugs for CRC. In vivo drug response was examined with paired PDX mouse models. A double-blind co-clinical cohort study was carried out and the clinical outcomes of the enrolled patients were compared with the i-CR results. Resultsi-CR platform could be used to rapidly propagate primary colorectal tumor cells that represent individual patient tumors effectively by keeping the clonal heterogeneity and the genetic characteristics. Chemotherapy drug screenings with i-CR cells were comparable with that of PDX models. More importantly, i-CR results showed high accordance with the clinical outcomes of the enrolled CRC patients. Conclusioni-CR platform was capable to test and optimize therapeutic regimens pre-clinically, study cancer cell biology, and model tumor re-emergence to identify new targeted therapeutics from an effective personalized medicine standpoint.

The relationship between systemic inflammation, body composition and clinical outcomes in patients with operable colorectal cancer at low and medium to high nutritional risk.

Rationale: In accordance with ESPEN (European Society of Parenteral and Enteral Nutrition) guidelines, the combination of malnutrition screening tool (MUST)1, systemic inflammation (mGPS) and body composition (SMI and SMD) were examined in relation to clinical outcomes in patients undergoing surgery for colorectal cancer (CRC).

A Modified Tumor-Node-Metastasis Classification for Primary Operable Colorectal Cancer.

BackgroundThe American Joint Committee on Cancer (AJCC) 8th tumor-node-metastasis (TNM) classification for colorectal cancer (CRC) has limited ability to predict prognosis.MethodsWe included 45 379 eligible stage I-III CRC patients from the Surveillance, Epidemiology, and End Results Program. Patients were randomly assigned individually to a training (n = 31 772) or an internal validation cohort (n = 13 607). External validation was performed in 10 902 additional patients. Patients were divided according to T and N stage permutations. Survival analyses were conducted by a Cox proportional hazard model and Kaplan-Meier analysis, with T1N0 as the reference. Area under receiver operating characteristic curve and Akaike information criteria were applied for prognostic discrimination and model fitting, respectively. Clinical benefits were further assessed by decision curve analyses.ResultsWe created a modified TNM (mTNM) classification: stages I (T1-2N0-1a); IIA (T1N1b, T2N1b, T3N0); IIB (T1-2N2a-2b, T3N1a-1b, T4aN0); IIC (T3N2a, T4aN1a-2a, T4bN0); IIIA (T3N2b, T4bN1a); IIIB (T4aN2b, T4bN1b); and IIIC (T4bN2a-2b). In the internal validation cohort, compared with the AJCC 8th TNM classification, the mTNM classification showed superior prognostic discrimination (area under receiver operating characteristic curve = 0.675 vs 0.667, respectively; 2-sided P < .001) and better model fitting (Akaike information criteria = 70 937 vs 71 238, respectively). Similar findings were obtained in the external validation cohort. Decision curve analyses revealed that the mTNM had superior net benefits over the AJCC 8th TNM classification in the internal and external validation cohorts.ConclusionsThe mTNM classification provides better prognostic discrimination than AJCC 8th TNM classification, with good applicability in various populations and settings, to help better stratify stage I-III CRC patients into prognostic groups.

Effect of Baseline Characteristics and Tumor Burden on Vaspin Expression and Progressive Disease in Operable Colorectal Cancer.

Colorectal cancer is a highly heterogeneous malignancy in the Asian population, and it is considered an important prognostic factor for baseline characteristics, tumor burden, and tumor markers. This study investigated the effect of baseline characteristics and tumor burden on tumor marker expression and progressive disease in colorectal cancer by using partial least squares variance-based path modeling (PLS-PM). PLS-PM can be used to evaluate the complex relationship between prognostic variables and progressive disease status with a small sample of measurements and structural models. A total of 89 tissue samples of colorectal cancer were analyzed. Our results suggested that the expression of visceral adipose tissue-derived serpin (vaspin) is a potential indicator of colorectal cancer progression and may be affected by baseline characteristics such as age, sex, body mass index, and diabetes mellitus. Moreover, according to the characteristics of tumor burden, the expression of vaspin was generally higher in each progressive disease patient. The overall findings suggest that vaspin is a potential indicator of the progressive disease and may be affected by the baseline characteristics of patients.

Creation of a Novel Inflammation-Based Score for Operable Colorectal Cancer Patients.

AimSystemic inflammation has been implicated in the progression of patients with colorectal cancer (CRC). We evaluated the prognostic ability of a comprehensive score based on several inflammatory indexes in operable CRC patients.Patients and MethodsBetween July 2013 and September 2017, this study retrospectively identified 1279 CRC patients receiving radical surgery in Wuhan Union Hospital and randomly assigned them into training (N=921) and validation (N=358) sets. A novel score, the CRC-specific inflammatory index (CSII), was developed from a series of inflammatory indexes significantly associated with survival in patients with CRC. This novel score was then divided into three categories and compared to the well-known systematic inflammatory index (SII) and TNM stage. Finally, a survival nomogram was generated by combining the CSII and other informative clinical features.ResultsThe CSII-OS was calculated as 1.110×lg ALRI + 1.082×CAR + 0.792×PI, while CSII-DFS was 1.709×lg ALRI + 1.033×CAR based on multivariable Cox regression analysis. Patients with high CSII experienced a worse OS (HR=23.72, 95% CI, 11.30–49.78, P <0.001) and worse DFS (HR=15.62, 95% CI, 6.95–35.08, P <0.001) compared to those in CRC patients with low CSII. Moreover, ROC analyses showed that the CSII possessed excellent performance (AUC=0.859) in predicting OS and DFS. The AUC of the OS nomogram based on CSII, TNM stage, and chemotherapy was 0.897, while that of the DFS nomogram based on CSII, T stage, and TNM stage was 0.873. High-quality calibration curves in both OS and DFS nomograms were observed. Verification in the validation dataset showed results consistent with those in the training dataset.ConclusionThe CSII is a CRC-specific prognostic score based on the combination of available inflammatory indexes. High CSII is a strong predictor of worse survival outcomes. The CSII also exhibits better predictive performance compared to SII or TNM stage in operable CRC patients.

The relationship between computed tomography derived skeletal muscle index, psoas muscle index and clinical outcomes in patients with operable colorectal cancer.

Computed tomography-based measures of body composition are emerging as important prognostic factors for patients with colorectal cancer (CRC). The aim of this study was to examine the relationship between total skeletal muscle index (SMI), psoas muscle index (PMI) and clinical outcomes in patients with operable CRC. A retrospective cohort study of prospectively maintained database at Glasgow Royal Infirmary. CT image at L3 was carried out to assess total skeletal and psoas muscle areas and these were normalized for height squared to calculate SMI and PMI respectively. Patients were classified into high and low groups using calculated optimal thresholds and their relationship to clinical outcomes was studied using logistic regression analysis. Of the 1002 patients included, 55% were male, 50% had low SMI and 42% had low PMI. A moderate correlation was found between total skeletal muscle and psoas areas (rs=0.70, p<0.001). On univariate analysis, low SMI was associated with length of hospital stay (OR, 1.47; 95% CI, 1.15-1.89, p=0.002) and overall survival (HR, 2.29; 95% CI, 1.47-3.58, p<0.001). On multivariate analysis, low SMI was independently associated with length of hospital stay (HR 1.32; 95% CI, 1.02-1.70, p<0.05). On univariate analysis, low PMI was associated with length of hospital stay (OR, 1.34; 95% CI, 1.04-1.73, p<0.05) and overall survival (OR, 1.43; 95% CI, 1.10-1.86 p<0.01). On multivariate analysis, low PMI was not independently significant. The present study shows that though both total skeletal muscle index and psoas muscle index were directly associated and had prognostic value, total skeletal muscle index had independent prognostic value in patients with operable CRC.

The relationship between systemic inflammation, body composition and clinical outcomes in patients with operable colorectal cancer at low and medium to high nutritional risk

AbstractBackgroundIn accordance with European Society of Parenteral and Enteral Nutrition guidelines, the combination of malnutrition universal screening tool (MUST), systemic inflammation [modified Glasgow prognostic score (mGPS)] and body composition [skeletal muscle index (SMI) and skeletal muscle density (SMD)] were examined in relation to clinical outcomes in patients undergoing surgery for colorectal cancer (CRC).MethodsData were collected for stages I–III CRC patients from prospectively maintained data base at the academic department of surgery, Glasgow Royal Infirmary. From the initial sample of 1046, pre‐admission MUST score was available in 984 patients. The classification into low malnutrition risk (MUST = 0, n = 810) and moderate to high malnutrition risk (MUST 1 to ≥2, n = 174) groups and their relationship to systemic inflammatory response and body composition (SMI and SMD) with clinical outcomes were examined using univariate and multivariate analyses.ResultsCompared with those patients at low nutrition risk (MUST = 0), patients at moderate to high malnutrition risk (MUST 1 to ≥2) had an elevated mGPS (P &lt; 0.001), neutrophil lymphocyte ratio (NLR) (P &lt; 0.001), low SMI (P ≤ 0.001) and low SMD (P = 0.015). MUST was an important prognostic factor for length of hospital stay (P &lt; 0.001) and 3 years overall survival (P &lt; 0.001).In low malnutrition risk patients (MUST = 0), those who were systemically inflammed (mGPS 1/2, n = 187), had an elevated NLR (P &lt; 0.001), low SMI (P &lt; 0.001), low SMD (P &lt; 0.01), increased post‐operative complications (P &lt; 0.05), longer hospital stay &gt;7 days (P &lt; 0.001), and poorer 3 years survival (P &lt; 0.05) compared with those who were not systemically inflamed. On multivariate analysis, American Society of Anaesthesiologist (ASA) score (P &lt; 0.05) and mGPS (P &lt; 0.05) were independently associated with increased risk of clinical complications. ASA, mGPS, and NLR were independently associated with prolonged hospital stay (P &lt; 0.05, P &lt; 0.05, and P &lt; 0.001, respectively). ASA, tumour, node, metastasis stage, and mGPS were independently associated with overall survival (P &lt; 0.01, P &lt; 0.001, and P &lt; 0.05, respectively).In medium‐risk to high‐risk patients (MUST = 1/2), those who were systemically inflamed (mGPS 1/2, n = 75) had higher ASA (P &lt; 0.05), elevated NLR (P &lt; 0.01), low SMI (P = 0.05) and low SMD (P &lt; 0.05), increased length of hospital stay (P &lt; 0.05), and poorer 3 years survival (P &lt; 0.01), compared with those who were not systemically inflamed.ConlusionsA small proportion of patients with primary operable CRC was at nutrition risk as defined by MUST alone in both low risk nutrition patients and medium/high risk nutrition patients. The systemic inflammatory response was associated with lower SMI, lower SMD, and poor clinical outcomes. The systemic inflammatory response is an important measure in the nutritional assessment of patients undergoing surgery for CRC.